RESUMO
RESUMEN Introducción: El Virus de Papiloma Humano se considera un factor clave en el desarrollo de lesiones cérvico uterinas. No obstante, la infección per se no es suficiente para desarrollar todos los eventos carcinogénicos, de manera que estos podrían estar regulados por vías de señalización celular. Las señales transmitidas hacia el interior de la célula, se producen a través de cascadas de señalización, en las que intervienen numerosas proteínas que ganan y/o pierden su actividad biológica, regulando así el metabolismo, la transcripción y traducción de genes. Objetivo: Proveer información actualizada sobre las vías de señalización TLRs, Wnt/ß-catenina y PI3K/Akt implicadas en la carcinogénesis cervical. Métodos: Se realizó una revisión de la literatura especializada mediante artículos originales y revisiones publicadas en bases de datos pertenecientes a los sitios web PubMed, Google Scholar, EBSCO y NCBI, en idiomas español e inglés. Resultados: Se constató que la vía TLR juega un rol clave en el combate a virus, bacterias y otras infecciones, además de poseer actividad inmune antitumoral. La vía Wnt/ß-catenina participa en varios procesos biológicos como la diferenciación, migración y adhesión celular, mientras que, PI3K/Akt está relacionada con el crecimiento, la motilidad y la supervivencia celular. Conclusiones: La activación o desregulación de algunos componentes de estas vías están implicadas en la proliferación incontrolada de células tumorales, evento importante en la carcinogénesis cervical(AU)
ABSTRACT Introduction: Human papillomavirus is considered a key factor in the development of uterine cervical lesions. However, infection per se is not enough to develop all carcinogenic events, so that these could be regulated by cell signaling pathways. The signals transmitted into the cell are produced through signaling cascades, which involve numerous proteins that gain and, or lose their biological activity, thus regulating the metabolism, transcription and translation of genes. Objective: To provide updated information on TLRs, Wnt / ß-catenin and PI3K / Akt signaling pathways involved in cervical carcinogenesis. Methods: A review of specialized literature was carried out through original articles and reviews published in PubMed, Google Scholar, EBSCO databases and NCBI websites, in Spanish and English languages. Results: TLR pathway was found to play a key role in the fight against viruses, bacteria and other infections, as well as having antitumor immune activity. The Wnt / ß-catenin pathway participates in several biological processes such as cell differentiation, migration and adhesion, while PI3K / Akt is related to cell growth, motility and survival. Conclusions: The activation or deregulation of some components of these pathways are involved in uncontrolled proliferation of tumor cells, an important event in cervical carcinogenesis(AU)
Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Infecções por Papillomavirus/etiologia , Carcinogênese/patologia , Literatura de Revisão como Assunto , Bases de Dados BibliográficasRESUMO
BACKGROUND/AIM: Host molecules disturbed by human papillomavirus (HPV) oncoproteins have been shown to be potential biomarkers of cervical carcinogenesis and represent an alternative or supplementary aid to cytological testing and HPV detection. The miR-203 and one of its targets, ΔNp63, are known to be host molecules that interact with each other to control the proliferation and differentiation of keratinocytes; both have been found to be dysregulated in many cancers. As the role of p63 and miR-203 in cervical carcinogenesis is not yet well-understood, we have, thus, decided to evaluate the changes of expression of both in cervical carcinogenesis. MATERIALS AND METHODS: This study was carried out by obtaining quantitative polymerase chain reaction (qPCR) data from cervical biopsies. RESULTS: miR-203 and ΔNp63 displayed a similar expression pattern across cervical tissues and both targets showed statistically significant differences between low-grade squamous intraepithelial lesion (LSIL) x high-grade squamous intraepithelial lesion (HSIL); HSIL x Cancer. Additionally, we did not observe an inverse correlation between ΔNp63 mRNA and miR-203 levels as expected but, rather, a positive correlation between cervical tissues. CONCLUSION: Although preliminary, the expression levels of ΔNp63 mRNA and miR-203 seem to be promising for cervical cancer screening. In addition, positive correlation between miR-203 and ΔNp63 expression suggests the possible existence of some indirect pathways. However, further studies are needed to clarify the role of ΔNp63 and miR-203 in cervical carcinogenesis and, thus, determine how they can be applied in new strategies for diagnosis.